B30-01 Comprehensive Proteomic Landscape of a Soot Inhalation Surrogate Model of Deployment Associated Chronic Obstructive Pulmonary Disease and Emphysema

Abstract Rationale Deployment-related respiratory diseases occur after exposure to air-burning fires and combustion processes that produce carbonaceous hazards like carbonaceous ultrafine particles, a key component of soot. Occupations such as firefighting and military service often lead to exposure to nanosized carbon-containing soot (nCB), often surpassing permissible UFP levels, and resulting in chronic bronchitis, decreased lung function, and COPD/emphysema. The lung clears carbon black particles through alveolar macrophages (AMs), but the impact of nCB exposure on AM function remains poorly understood. We created a surrogate model to study airborne hazard-induced emphysema, using nanosized carbon black particles to mimic soot and investigate the mechanisms behind deployment-related COPD/emphysema. Methods Two subacute intratracheal exposures of nCB were performed on 12-week-old mice, representing early 20s in human age, and the mice were sacrificed after a week and after wait period of 8 weeks, corresponding to early 30s in human age, and the lungs were analyzed. Whole-proteomic analysis using LC/MS mass spectrometry, histological analysis, and lung functions were performed. The Institutional Animal Care and Use Committee approved all animal protocols at the University of Alabama at Birmingham (UAB). Results We observed increased inflammation marked by a higher presence of lymphocytes in the nCB-exposed mouse lung. Histology analysis showed alveolar macrophages filled with engulfed nCBs and emphysema in the nCB-exposed lungs due to increased cell death. The proteomic data identified 1,894 proteins across the samples. We identified 178 proteins that were significantly differentially expressed in the lung proteome of mice exposed to nCB. Both histology and proteomic analysis demonstrated emphysema and pathways related to increased cell death. The top 39 differentially expressed proteins, analyzed by functional enrichment, were involved in dysregulation of ubiquitination, reduced vesicle trafficking, endosome formation, and calcium signaling. The differentially expressed proteins in the nCB group are linked to emphysema development, including processes like cell death and inflammasome activation. Conclusion Sub-acute lung exposures to nCB induced airway remodeling and emphysema later in life, showing a distinct protein expression pattern with increased cell death pathways and tissue damage. Inflammasome activation and suppression of endosomal and lysosomal-related proteins suggest that lung macrophages become exhausted after nCB exposure, reaching their capacity to clear nCB. We are conducting a comparative analysis of the progression of inflammation and emphysema in nCB exposure at early and late phase post-exposure, ongoing research focuses on their role in the development of COPD and emphysema. This abstract is funded by: NIEHS/NIH